Cargando…
84 Immuno-Safety of Recombinant Human C1 Inhibitor in Patients With Hereditary Angioedema: An Integrated Analysis
BACKGROUND: Recombinant C1 inhibitor (rhC1INH) is a novel therapeutic option for the treatment of acute angioedema attacks in patients with hereditary angioedema (HAE). The amino acid sequence of rhC1INH is identical to that of endogenous C1INH. However, any recombinant protein may elicit antibodies...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
World Allergy Organization Journal
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3512662/ http://dx.doi.org/10.1097/01.WOX.0000411829.92623.61 |
_version_ | 1782251772566306816 |
---|---|
author | Hack, Erik Relan, Anurag Kaufman, Leonard Pijpstra, Rienk |
author_facet | Hack, Erik Relan, Anurag Kaufman, Leonard Pijpstra, Rienk |
author_sort | Hack, Erik |
collection | PubMed |
description | BACKGROUND: Recombinant C1 inhibitor (rhC1INH) is a novel therapeutic option for the treatment of acute angioedema attacks in patients with hereditary angioedema (HAE). The amino acid sequence of rhC1INH is identical to that of endogenous C1INH. However, any recombinant protein may elicit antibodies against the protein and/or host related impurities (HRI). Clinical consequences of these antibodies can theoretically range from no clinical symptoms to allergic reactions and reduced C1INH activity due to neutralizing antibodies. OBJECTIVE: To analyze the immuno-safety of rhC1INH in symptomatic patients with HAE. METHODS: Plasma samples were collected pre-treatment and 22 and 90 days post-treatment of an acute angioedema attack. Plasma samples were tested for the presence of antibodies against plasma-derived C1INH and rhC1INH using 6 different, validated enzyme-linked immunosorbent assays (ELISAs), to detect IgM, IgG and IgA antibodies against plasma-derived C1INH or rhC1INH. Antibodies against HRI in plasma samples were measured in an ELISA testing for all antibody classes. Plasma samples from normal healthy controls and HAE patients, never exposed to rhC1INH, were used to estimate cut off levels of the assays. Plasma samples with antibody levels above the cut-off level in the screening assays were tested in confirmatory displacement assay in case of anti-HRI antibodies and in an assay for neutralizing antibodies in case of antibodies against C1INH. RESULTS: Data from 155 symptomatic HAE patients having received a total of 424 administrations of rhC1INH were analyzed. The frequency of anti-C1INH antibody levels above the assay cut-off was low and similar in pre- and post-exposure samples (1.7 and 1.8%, respectively). Results above the assay cut-off were sporadic and transient. Occurrence of anti-C1INH antibodies did not correlate with repeated treatment or time since last treatment. No neutralizing antibodies were detected. A total of 5/155 (3%) rhC1INH-treated patients had confirmed anti-HRI antibodies; these included 1 patient with presence of anti-HRI antibodies prior to exposure to rhC1INH. The presence of anti-C1INH and anti-HRI antibodies was not associated with clinical symptoms. The presence of anti-C1INH antibodies did not affect clinical efficacy. CONCLUSIONS: rhC1INH used for the treatment of acute HAE attacks has a low potential to induce antibodies and has a reassuring immuno-safety profile. |
format | Online Article Text |
id | pubmed-3512662 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | World Allergy Organization Journal |
record_format | MEDLINE/PubMed |
spelling | pubmed-35126622012-12-21 84 Immuno-Safety of Recombinant Human C1 Inhibitor in Patients With Hereditary Angioedema: An Integrated Analysis Hack, Erik Relan, Anurag Kaufman, Leonard Pijpstra, Rienk World Allergy Organ J Abstracts of the XXII World Allergy Congress BACKGROUND: Recombinant C1 inhibitor (rhC1INH) is a novel therapeutic option for the treatment of acute angioedema attacks in patients with hereditary angioedema (HAE). The amino acid sequence of rhC1INH is identical to that of endogenous C1INH. However, any recombinant protein may elicit antibodies against the protein and/or host related impurities (HRI). Clinical consequences of these antibodies can theoretically range from no clinical symptoms to allergic reactions and reduced C1INH activity due to neutralizing antibodies. OBJECTIVE: To analyze the immuno-safety of rhC1INH in symptomatic patients with HAE. METHODS: Plasma samples were collected pre-treatment and 22 and 90 days post-treatment of an acute angioedema attack. Plasma samples were tested for the presence of antibodies against plasma-derived C1INH and rhC1INH using 6 different, validated enzyme-linked immunosorbent assays (ELISAs), to detect IgM, IgG and IgA antibodies against plasma-derived C1INH or rhC1INH. Antibodies against HRI in plasma samples were measured in an ELISA testing for all antibody classes. Plasma samples from normal healthy controls and HAE patients, never exposed to rhC1INH, were used to estimate cut off levels of the assays. Plasma samples with antibody levels above the cut-off level in the screening assays were tested in confirmatory displacement assay in case of anti-HRI antibodies and in an assay for neutralizing antibodies in case of antibodies against C1INH. RESULTS: Data from 155 symptomatic HAE patients having received a total of 424 administrations of rhC1INH were analyzed. The frequency of anti-C1INH antibody levels above the assay cut-off was low and similar in pre- and post-exposure samples (1.7 and 1.8%, respectively). Results above the assay cut-off were sporadic and transient. Occurrence of anti-C1INH antibodies did not correlate with repeated treatment or time since last treatment. No neutralizing antibodies were detected. A total of 5/155 (3%) rhC1INH-treated patients had confirmed anti-HRI antibodies; these included 1 patient with presence of anti-HRI antibodies prior to exposure to rhC1INH. The presence of anti-C1INH and anti-HRI antibodies was not associated with clinical symptoms. The presence of anti-C1INH antibodies did not affect clinical efficacy. CONCLUSIONS: rhC1INH used for the treatment of acute HAE attacks has a low potential to induce antibodies and has a reassuring immuno-safety profile. World Allergy Organization Journal 2012-02-17 /pmc/articles/PMC3512662/ http://dx.doi.org/10.1097/01.WOX.0000411829.92623.61 Text en Copyright © 2012 by World Allergy Organization |
spellingShingle | Abstracts of the XXII World Allergy Congress Hack, Erik Relan, Anurag Kaufman, Leonard Pijpstra, Rienk 84 Immuno-Safety of Recombinant Human C1 Inhibitor in Patients With Hereditary Angioedema: An Integrated Analysis |
title | 84 Immuno-Safety of Recombinant Human C1 Inhibitor in Patients With Hereditary Angioedema: An Integrated Analysis |
title_full | 84 Immuno-Safety of Recombinant Human C1 Inhibitor in Patients With Hereditary Angioedema: An Integrated Analysis |
title_fullStr | 84 Immuno-Safety of Recombinant Human C1 Inhibitor in Patients With Hereditary Angioedema: An Integrated Analysis |
title_full_unstemmed | 84 Immuno-Safety of Recombinant Human C1 Inhibitor in Patients With Hereditary Angioedema: An Integrated Analysis |
title_short | 84 Immuno-Safety of Recombinant Human C1 Inhibitor in Patients With Hereditary Angioedema: An Integrated Analysis |
title_sort | 84 immuno-safety of recombinant human c1 inhibitor in patients with hereditary angioedema: an integrated analysis |
topic | Abstracts of the XXII World Allergy Congress |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3512662/ http://dx.doi.org/10.1097/01.WOX.0000411829.92623.61 |
work_keys_str_mv | AT hackerik 84immunosafetyofrecombinanthumanc1inhibitorinpatientswithhereditaryangioedemaanintegratedanalysis AT relananurag 84immunosafetyofrecombinanthumanc1inhibitorinpatientswithhereditaryangioedemaanintegratedanalysis AT kaufmanleonard 84immunosafetyofrecombinanthumanc1inhibitorinpatientswithhereditaryangioedemaanintegratedanalysis AT pijpstrarienk 84immunosafetyofrecombinanthumanc1inhibitorinpatientswithhereditaryangioedemaanintegratedanalysis |